A neurotoxin from Lathyrus sativus seeds (beta-N-oxalyl-L-alpha, beta-diaminopropionic acid) is believed responsible for the crippling human disease known as neurolathyrism. We have shown that the neurotoxin is a potent antagonist of L-glutamic acid in yeast-- an observation of interest in connection with the postulated role of glutamate as an excitatory neurotransmitter in the central nervous system of vertebrates. The yeast strains most sensitive to the toxin are those with the largest intracellular amino acid pools, of which glutamate is the major component. Attempts to study neurolathyrism in experimental animals have been handicapped by the immunity of animals to the toxin--unless the toxin is injected directly into brain or spinal cord or is injected as a single large dose into an animal with an immature blood-brain barrier. Why adult humans are vulnerable to the effects of the toxin is unknown. However, human neurolathyrism occurs only after many months on a diet high in L. sativus seeds, low in calories and poor in protein quality. We suggest that sensitivity to the neurotoxin depends in animals and in humans (as it does in yeast) upon the size of the amino acid reserves. We plan 1) to explore fully the specificity of beta-N-oxalyl-L-alpha, beta-diaminopropionic acid with regard to its site of action in yeast and in animals, 2) to investigate the relationship of amino acid nutrition to toxicity of beta-N-oxalyl-L-alpha, beta-diaminopropionic acid in an experimental animal, 3) to investigate the absorption, excretion, tissue distribution, subcellular distribution and metabolic fate of the toxin and 4) to investigate the relationship of its glutamate-antagonizing properties to its neurotoxicity.